Can Xarelto (rivaroxaban), omeprazole, or meloxicam cause hypertension (HTN)?

Can Xarelto, Omeprazole, or Meloxicam Cause Hypertension?

Meloxicam and omeprazole can potentially cause or exacerbate hypertension, while Xarelto (rivaroxaban) is not associated with causing hypertension.

Meloxicam and Hypertension Risk

Meloxicam, like other NSAIDs, can elevate blood pressure through multiple mechanisms including sodium retention, activation of the renin-angiotensin-aldosterone system, and alteration of vascular tone 1.

• The 2024 ESC Guidelines explicitly identify NSAIDs as a cause of drug-induced hypertension and recommend careful monitoring in patients taking these medications 2.
• A systematic review found that meloxicam increases composite cardiovascular risk (OR 1.14; 95% CI 1.04-1.25), primarily through vascular effects (OR 1.35; 95% CI 1.18-1.55), though this risk is lower compared to other NSAIDs like rofecoxib, indomethacin, and diclofenac 3.
• The vascular risk associated with meloxicam can manifest as elevated blood pressure, particularly with chronic use 3.

Clinical Management for Meloxicam

• Monitor blood pressure regularly in patients taking meloxicam, especially those with pre-existing hypertension 2, 1.
• Consider discontinuing meloxicam if blood pressure becomes difficult to control or increases significantly 1.
• Use the lowest effective dose for the shortest duration necessary 3.
• Meloxicam does not require dose adjustment in mild-to-moderate renal impairment, but blood pressure monitoring remains essential 4.

Omeprazole and Hypertension Risk

Emerging evidence suggests omeprazole may cause hypertension, though this association is not yet widely recognized in major regulatory guidelines 5.

• A 2024 analysis of the WHO global pharmacovigilance database (VigiBase) identified 1,043 cases of hypertension related to omeprazole from 36 countries, with a statistical signal triggered (IC025: 0.12) 5.
• Among these cases, 65% were reported as serious and 10.6% as fatal 5.
• Positive dechallenge occurred in 85 cases (hypertension resolved after stopping omeprazole) and positive rechallenge in 14 cases (hypertension recurred after restarting), with a median time-to-onset of 2 days 5.
• In 122 cases where omeprazole was the sole drug administered, the temporal relationship and reversibility strongly suggest causality 5.

Clinical Management for Omeprazole

• Monitor blood pressure when initiating omeprazole, particularly in patients with pre-existing hypertension or cardiovascular risk factors 5.
• Consider alternative acid suppression strategies (H2-receptor antagonists) if hypertension develops or worsens on omeprazole 5.
• The rapid onset (median 2 days) means blood pressure changes may occur early in therapy 5.

Xarelto (Rivaroxaban) and Hypertension

Rivaroxaban does not cause hypertension and is not listed among medications that induce elevated blood pressure 2.

• The 2013 NCCN guidelines and 2020 ESC guidelines on anticoagulation do not identify hypertension as an adverse effect of rivaroxaban 2.
• Rivaroxaban's primary concerns relate to bleeding risk, renal function (avoid if CrCl <30 mL/min), and drug interactions via CYP3A4 metabolism 2.
• The 2024 ESC hypertension guidelines do not list anticoagulants among drugs causing drug-induced hypertension 2.

Key Clinical Pitfalls to Avoid

• Do not overlook NSAIDs as a reversible cause of resistant hypertension – meloxicam and other NSAIDs are frequently missed contributors to uncontrolled blood pressure 2, 1.
• Do not assume all proton pump inhibitors are equivalent – while omeprazole shows emerging hypertensive risk, this may not apply equally to all PPIs 5.
• Do not confuse anticoagulant precautions with hypertensive effects – rivaroxaban requires monitoring for bleeding and renal function, not blood pressure elevation 2.
• Monitor for drug-drug interactions – combining meloxicam with ACE inhibitors or ARBs can reduce their antihypertensive efficacy and increase renal risk 1.